Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis

Hanyao Huang, Weiyi Pan, Yifan Wang, Hye Sung Kim, Dan Shao, Baoding Huang, Tzu-Chieh Ho, Yeh-Hsing Lao, Chai Hoon Quek, Jiayu Shi, Qianming Chen, Bing Shi, Shengmin Zhang (), Lei Zhao () and Kam W. Leong ()
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Hanyao Huang: Sichuan University
Weiyi Pan: Sichuan University
Yifan Wang: Huazhong University of Science and Technology
Hye Sung Kim: Columbia University
Dan Shao: Columbia University
Baoding Huang: Columbia University
Tzu-Chieh Ho: Columbia University
Yeh-Hsing Lao: Columbia University
Chai Hoon Quek: Columbia University
Jiayu Shi: The University of Michigan
Qianming Chen: Sichuan University
Bing Shi: Sichuan University
Shengmin Zhang: Huazhong University of Science and Technology
Lei Zhao: Sichuan University
Kam W. Leong: Columbia University

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.

Date: 2022
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DOI: 10.1038/s41467-022-33492-6

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